PTP4A2

Summary

PTP4A2 (protein tyrosine phosphatase 4A2, HGNC:9635) is a protein-coding gene on chromosome 1p35.2, encoding Protein tyrosine phosphatase type IVA 2 (Q12974). Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. It is a selective cancer dependency (DepMap: 17.9% of cell lines).

The protein encoded by this gene belongs to a small class of the protein tyrosine phosphatase (PTP) family. PTPs are cell signaling molecules that play regulatory roles in a variety of cellular processes. PTPs in this class contain a protein tyrosine phosphatase catalytic domain and a characteristic C-terminal prenylation motif. This PTP has been shown to primarily associate with plasmic and endosomal membrane through its C-terminal prenylation. This PTP was found to interact with the beta-subunit of Rab geranylgeranyltransferase II (beta GGT II), and thus may function as a regulator of GGT II activity. Overexpression of this gene in mammalian cells conferred a transformed phenotype, which suggested its role in tumorigenesis. Alternatively spliced transcript variants have been described. Related pseudogenes exist on chromosomes 11, 12 and 17.

Source: NCBI Gene 8073 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 30 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 17.9% of screened cell lines
• MANE Select transcript: NM_080391

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9635
Approved symbol	PTP4A2
Name	protein tyrosine phosphatase 4A2
Location	1p35.2
Locus type	gene with protein product
Status	Approved
Aliases	HU-PP-1, PTPCAAX2, OV-1, ptp-IV1a, PRL-2, PRL2
Ensembl gene	ENSG00000184007
Ensembl biotype	protein_coding
OMIM	601584
Entrez	8073

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 8 protein_coding, 8 protein_coding_CDS_not_defined, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000457805, ENST00000468531, ENST00000470404, ENST00000475464, ENST00000484483, ENST00000489313, ENST00000494444, ENST00000524384, ENST00000526960, ENST00000528253, ENST00000528840, ENST00000529477, ENST00000532001, ENST00000532289, ENST00000533408, ENST00000534796, ENST00000602683, ENST00000602725, ENST00000647444, ENST00000649841

RefSeq mRNA: 6 — MANE Select: NM_080391 NM_001195100, NM_001195101, NM_001369858, NM_001369859, NM_001369860, NM_080391

CCDS: CCDS348, CCDS53292, CCDS59193

Canonical transcript exons

ENST00000647444 — 6 exons

Exon	Start	End
ENSE00001811309	31906421	31908960
ENSE00002188842	31918970	31919658
ENSE00003631447	31911696	31911826
ENSE00003692122	31910038	31910112
ENSE00003784401	31915895	31915987
ENSE00003824320	31937987	31938368

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 140.8388 / max 1442.8566, expressed in 1828 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11511	136.9970	1828
11510	2.0066	1245
11509	1.1755	671
11501	0.4916	256
11508	0.0974	39
11507	0.0705	20

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	99.77	gold quality
medial globus pallidus	UBERON:0002477	99.74	gold quality
inferior vagus X ganglion	UBERON:0005363	99.71	gold quality
globus pallidus	UBERON:0001875	99.70	gold quality
palpebral conjunctiva	UBERON:0001812	99.53	gold quality
middle frontal gyrus	UBERON:0002702	99.49	gold quality
cranial nerve II	UBERON:0000941	99.47	gold quality
lateral globus pallidus	UBERON:0002476	99.46	gold quality
parotid gland	UBERON:0001831	99.45	gold quality
medulla oblongata	UBERON:0001896	99.44	gold quality
ventral tegmental area	UBERON:0002691	99.44	gold quality
subthalamic nucleus	UBERON:0001906	99.42	gold quality
inferior olivary complex	UBERON:0002127	99.39	gold quality
thymus	UBERON:0002370	99.38	gold quality
superior vestibular nucleus	UBERON:0007227	99.38	gold quality
endothelial cell	CL:0000115	99.36	gold quality
sperm	CL:0000019	99.35	gold quality
germinal epithelium of ovary	UBERON:0001304	99.35	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.35	gold quality
male germ cell	CL:0000015	99.33	gold quality
pylorus	UBERON:0001166	99.32	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.32	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.31	gold quality
cartilage tissue	UBERON:0002418	99.28	gold quality
spinal cord	UBERON:0002240	99.27	gold quality
midbrain	UBERON:0001891	99.26	gold quality
pericardium	UBERON:0002407	99.26	gold quality
substantia nigra	UBERON:0002038	99.24	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.21	gold quality
epithelium of nasopharynx	UBERON:0001951	99.21	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-6505	yes	2192.03
E-CURD-79	yes	2062.75
E-HCAD-4	yes	57.57
E-MTAB-8142	yes	25.04
E-CURD-122	yes	6.29
E-MTAB-6678	yes	4.14
E-GEOD-106540	no	661.65
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

108 targeting PTP4A2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-548D-3P	99.87	70.67	4362

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 17.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 19)

• PRL phosphatases increase cell proliferation by stimulating progression from G1 into S phase (PMID:14643450)
• PRL-2 mRNA expression was not significantly higher in malignant compared to benign breast tissue. (PMID:16832410)
• PRL-2 was expressed heavily in almost every tissue and cell type examined. Widespread expression of PRL-2 in multiple organ systems suggests an important functional role for these enzymes in normal tissue homeostasis. (PMID:16957164)
• Colonic adenocarcinoma cells have the ability to produce PTP4A1, PTP4a2, and PTP4A3, which may relate to the lymph node metastasis of colonic adenocarcinoma. (PMID:17440740)
• PRL-2 can promote cell adhesion and invasion activity of human hepatocellular carcinoma cells. (PMID:17666324)
• Mouse pre-B-cells transfected with human PRL-2 had higher growth responses to Epo or IL-3, shorter cell cycle, less Epo requirement for survival, more cell migration, less cell adhesion, change to an immature cell morphology, & more Bmi-1 expression. (PMID:20226699)
• Overexpression of the protein tyrosine phosphatase PRL-2 correlates with breast tumor formation and progression. (PMID:20841483)
• Results suggest a model in which PRL-2 promotes cell migration and invasion through an ERK1/2-dependent signaling pathway. (PMID:21765462)
• PRL-2 plays an important role in lung cancer and can be a biomarker of lung cancer, substituting for the function of other PRLs. (PMID:21993571)
• Studies indicate that PRL-1 and PRL-2 and PRL-3 are oncogenes and belong to the few phosphatases that lead to the development of cancer. (PMID:22413991)
• Results suggest that TRP32 maintains the reduced state of PRL and thus regulates the biological function of PRL. (PMID:23362275)
• PTP4A2 expression is correlated with overall survival in progestin receptor-positive breast carcinomas. (PMID:23568563)
• Our findings highlight the important role of miR-29c in regulating CRC EMT via GSK-3b/b-catenin signaling by targeting GNA13 and PTP4A and provide new insights into the metastatic basis of colorectal cancer (PMID:25193986)
• study identified a critical role for PRL2 phosphatase in the proliferation and survival of human T-ALL cells; demonstrated that PRL2 is important for the leukemogenic potential of oncogenic NOTCH1 in vivo (PMID:27872499)
• identified a critical role for PRL2 phosphatase in the proliferation and survival of human AML cells. Further, we demonstrated that PRL2 is essential for the leukemogenic potential of AML1-ETO9a in vivo (PMID:28220038)
• altered PRL-2 expression leads to metabolic reprogramming of the cells. These findings uncover a magnesium-sensitive mechanism controlling PRL expression, which plays a role in cellular bioenergetics (PMID:30718434)
• A FRET-based screening method to detect potential inhibitors of the binding of CNNM3 to PRL2. (PMID:32733084)
• Mechanism of PRL2 phosphatase-mediated PTEN degradation and tumorigenesis. (PMID:32788364)
• This study established the existence of a magnesium transporter protein complex (PTP4A2/CNNM3/TRPM7) governing the cellular uptake of this divalent cation. Moreover, PTP4A2 acts as a magnesium biosensor, controlling the activity of this complex to reprogram cellular metabolism. (PMID:36972446)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptp4a2b	ENSDARG00000035676
danio_rerio	ptp4a2a	ENSDARG00000087443
mus_musculus	Ptp4a2	ENSMUSG00000028788
rattus_norvegicus	Ptp4a2	ENSRNOG00000050044
drosophila_melanogaster	PRL-1	FBGN0024734
caenorhabditis_elegans		WBGENE00004184

Paralogs (8): CDC14A (ENSG00000079335), CDC14B (ENSG00000081377), CDKN3 (ENSG00000100526), PALD1 (ENSG00000107719), PTP4A1 (ENSG00000112245), PTPDC1 (ENSG00000158079), PTP4A3 (ENSG00000184489), CDC14C (ENSG00000218305)

Protein

Protein identifiers

Protein tyrosine phosphatase type IVA 2 — Q12974 (reviewed: Q12974)

Alternative names: HU-PP-1, OV-1, PTP(CAAXII), Protein-tyrosine phosphatase 4a2, Protein-tyrosine phosphatase of regenerating liver 2

All UniProt accessions (6): E9PJC0, E9PL34, E9PML8, E9PMY3, E9PRR9, Q12974

UniProt curated annotations — full annotation on UniProt →

Function. Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. Promotes tumors. Inhibits geranylgeranyl transferase type II activity by blocking the association between RABGGTA and RABGGTB.

Subunit / interactions. In contrast to PTP4A1 and PTP4A3, does not interact with tubulin. Interacts with RABGGTB.

Subcellular location. Cell membrane. Early endosome. Cytoplasm.

Tissue specificity. Ubiquitously expressed, with highest levels in skeletal muscle, heart and thymus. Overexpressed in prostate tumor tissue.

Post-translational modifications. Farnesylated. Farnesylation is required for membrane targeting and for interaction with RABGGTB. Unfarnesylated forms are redirected to the nucleus and cytosol.

Activity regulation. Inhibited by sodium orthovanadate and pentamidine.

Miscellaneous. A processed pseudogene with 96% sequence identity was found in the BRCA1 (113705) region of 17q21.

Similarity. Belongs to the protein-tyrosine phosphatase family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q12974-1	1, Ptp-IV1a, Ptp-IV1b	yes
Q12974-2	2, PTP4Ar
Q12974-3	3
Q12974-4	4

RefSeq proteins (6): NP_001182029, NP_001182030, NP_001356787, NP_001356788, NP_001356789, NP_536316* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000242	PTP_cat	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR003595	Tyr_Pase_cat	Domain
IPR020422	TYR_PHOSPHATASE_DUAL_dom	Domain
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR050561	PTP	Family

Pfam: PF00102

Catalyzed reactions (Rhea), 1 shown:

• O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)

UniProt features (33 total): strand 7, helix 6, splice variant 4, sequence conflict 3, mutagenesis site 2, active site 2, binding site 2, chain 1, propeptide 1, domain 1, turn 1, modified residue 1, lipid moiety-binding region 1, disulfide bond 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6WUR	X-RAY DIFFRACTION	2.88
5K23	X-RAY DIFFRACTION	2.96
5K22	X-RAY DIFFRACTION	3
5K25	X-RAY DIFFRACTION	3.05

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12974-F1	90.78	0.83

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 69 (proton donor); 101 (phosphocysteine intermediate)

Ligand- & substrate-binding residues (2): 102–107; 107

Post-translational modifications (2): 164, 164

Disulfide bonds (1): 46–101

Mutagenesis-validated functional residues (2):

Position	Phenotype
164–167	locates in the nucleus and cytosol. no interaction with rabggtb.
165	no effect on interaction with rabggtb.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8873719	RAB geranylgeranylation

MSigDB gene sets: 253 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, YANG_BREAST_CANCER_ESR1_BULK_UP, MORF_SNRP70, MORF_UBE2I, PID_PRL_SIGNALING_EVENTS_PATHWAY, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, HSIAO_HOUSEKEEPING_GENES, ATGTTAA_MIR302C, MORF_TERF1, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, MORF_CCNI, BLALOCK_ALZHEIMERS_DISEASE_UP, SCHLOSSER_SERUM_RESPONSE_DN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, DOUGLAS_BMI1_TARGETS_UP

GO Biological Process (2): protein dephosphorylation (GO:0006470), dephosphorylation (GO:0016311)

GO Molecular Function (5): protein tyrosine phosphatase activity (GO:0004725), enzyme inhibitor activity (GO:0004857), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (7): nucleus (GO:0005634), cytoplasm (GO:0005737), early endosome (GO:0005769), cytosol (GO:0005829), plasma membrane (GO:0005886), endosome (GO:0005768), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
catalytic activity	2
dephosphorylation	1
protein modification process	1
phosphate-containing compound metabolic process	1
phosphoprotein phosphatase activity	1
enzyme regulator activity	1
molecular function inhibitor activity	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
endosome	1
cytoplasm	1
membrane	1
cell periphery	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

992 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTP4A2	CNNM3	Q8NE01	962
PTP4A2	PTS	Q03393	897
PTP4A2	IL17RD	Q8NFM7	768
PTP4A2	NIPAL3	Q6P499	640
PTP4A2	NIPAL2	Q9H841	635
PTP4A2	NIPAL1	Q6NVV3	627
PTP4A2	NIPAL4	Q0D2K0	610
PTP4A2	NIPA2	Q8N8Q9	597
PTP4A2	SMR3A	Q99954	541
PTP4A2	DUSP22	Q9NRW4	509
PTP4A2	ARL15	Q9NXU5	499
PTP4A2	BCAR1	P56945	470
PTP4A2	CNNM4	Q6P4Q7	459
PTP4A2	ENO1	P06733	431
PTP4A2	ALB	P02768	420

IntAct

41 interactions, top by confidence:

A	B	Type	Score
CNNM1	PTP4A2	psi-mi:“MI:0915”(physical association)	0.760
PTP4A2	CNNM1	psi-mi:“MI:0915”(physical association)	0.760
PTP4A2	CNNM4	psi-mi:“MI:0914”(association)	0.740
PTP4A2	PTP4A3	psi-mi:“MI:0914”(association)	0.640
RABGGTB	PIPSL	psi-mi:“MI:0914”(association)	0.530
CYP8B1	TACSTD2	psi-mi:“MI:0914”(association)	0.530
PCDHB5	RPL23	psi-mi:“MI:0914”(association)	0.530
GPAA1	PTP4A2	psi-mi:“MI:0914”(association)	0.530
PTP4A1	PSMD3	psi-mi:“MI:0914”(association)	0.420
PTP4A2	USP11	psi-mi:“MI:2364”(proximity)	0.420
	TK2	psi-mi:“MI:0915”(physical association)	0.400
PTP4A2	MLH1	psi-mi:“MI:0915”(physical association)	0.370
Kif21b	TCP1	psi-mi:“MI:0914”(association)	0.350
PON2	ENTPD6	psi-mi:“MI:0914”(association)	0.350
GPAA1	ATP5F1B	psi-mi:“MI:0914”(association)	0.350
PTP4A2	SPTBN1	psi-mi:“MI:0914”(association)	0.350
BRICD5	POTEF	psi-mi:“MI:0914”(association)	0.350
FNTA	YKT6	psi-mi:“MI:0914”(association)	0.350
CACYBP	VPS37C	psi-mi:“MI:0914”(association)	0.350
CACYBP	PSMD11	psi-mi:“MI:0914”(association)	0.350
CAPRIN1	VPS37C	psi-mi:“MI:0914”(association)	0.350
CAPRIN1	SDCBP	psi-mi:“MI:0914”(association)	0.350
PTP4A1	NME6	psi-mi:“MI:0914”(association)	0.350
RABGGTB	SORBS3	psi-mi:“MI:0914”(association)	0.350
EIF4A1	SNAP23	psi-mi:“MI:0914”(association)	0.350

BioGRID (178): PTP4A2 (Affinity Capture-MS), PTP4A2 (Affinity Capture-MS), PTP4A2 (Affinity Capture-RNA), PTP4A2 (Affinity Capture-MS), CNNM4 (Affinity Capture-MS), GNB4 (Affinity Capture-MS), SPTAN1 (Affinity Capture-MS), SPTBN1 (Affinity Capture-MS), PTP4A1 (Affinity Capture-MS), CNNM1 (Affinity Capture-MS), PTP4A2 (Affinity Capture-MS), EFTUD1 (Affinity Capture-MS), CNNM4 (Affinity Capture-MS), CNNM2 (Affinity Capture-MS), PTP4A2 (Affinity Capture-MS)

ESM2 similar proteins: A0A7H0DN78, A2VDT1, O13632, O13926, O41136, O55737, O61722, O70274, O94526, P07239, P0DOQ5, P0DOQ6, P20495, P25044, P27574, P33825, P41415, P43568, P53208, P80994, Q02158, Q02256, Q08649, Q12385, Q12974, Q54DU9, Q5R7J8, Q5UNT1, Q5UQ96, Q5UQD2, Q5UQH3, Q5UR74, Q5XHB2, Q63739, Q6P9X4, Q78EG7, Q85297, Q86AT8, Q86IL4, Q8IG39

Diamond homologs: A0A0R4IVA4, A1L1R5, A2VDT1, A4D256, A6N3Q4, O60729, O61722, O70274, O75365, P81299, Q00684, Q12974, Q1LWL2, Q59NH8, Q5B323, Q5R7J8, Q63739, Q6GQT0, Q6NZK8, Q6P9X4, Q6PFY9, Q78EG7, Q86BN8, Q93096, Q9D658, Q9JLY7, Q9P7H1, Q9TSM6, Q9UNH5, Q9ZQP1, Q4CUJ8, Q4QEZ7, Q54DU9, Q86IL4, Q9FLZ5, Q6NT99, Q8T9S7, Q9BVJ7, A2A3K4, A7E379

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PTP4A2	up-regulates	CDK2	dephosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

30 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

793 predictions. Top by Δscore:

Variant	Effect	Δscore
1:31908961:C:CC	acceptor_gain	1.0000
1:31910030:ATAC:A	donor_loss	1.0000
1:31910031:TACT:T	donor_loss	1.0000
1:31910032:ACTC:A	donor_loss	1.0000
1:31910033:C:G	donor_loss	1.0000
1:31910033:CTCA:C	donor_gain	1.0000
1:31910034:T:TA	donor_loss	1.0000
1:31910036:A:AC	donor_gain	1.0000
1:31910036:AC:A	donor_loss	1.0000
1:31910036:ACTGT:A	donor_gain	1.0000
1:31910037:C:A	donor_loss	1.0000
1:31910037:C:CG	donor_gain	1.0000
1:31910037:CT:C	donor_gain	1.0000
1:31910037:CTG:C	donor_gain	1.0000
1:31910037:CTGT:C	donor_gain	1.0000
1:31910037:CTGTC:C	donor_gain	1.0000
1:31910109:TGCC:T	acceptor_gain	1.0000
1:31910110:GCC:G	acceptor_gain	1.0000
1:31910111:CC:C	acceptor_gain	1.0000
1:31910111:CCC:C	acceptor_gain	1.0000
1:31910111:CCCTG:C	acceptor_loss	1.0000
1:31910112:CC:C	acceptor_gain	1.0000
1:31910113:C:CA	acceptor_loss	1.0000
1:31910113:C:CC	acceptor_gain	1.0000
1:31910114:T:A	acceptor_loss	1.0000
1:31911698:T:A	donor_gain	1.0000
1:31915883:C:CT	donor_gain	1.0000
1:31915884:T:TT	donor_gain	1.0000
1:31915889:A:AC	donor_gain	1.0000
1:31915890:C:CC	donor_gain	1.0000

AlphaMissense

1087 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:31908919:A:G	L146S	1.000
1:31908949:C:T	G136E	1.000
1:31908950:C:G	G136R	1.000
1:31908950:C:T	G136R	1.000
1:31908954:T:A	R134S	1.000
1:31908954:T:G	R134S	1.000
1:31910040:T:A	R131S	1.000
1:31910040:T:G	R131S	1.000
1:31910041:C:G	R131T	1.000
1:31910044:A:T	I130K	1.000
1:31910053:A:T	V127D	1.000
1:31910107:G:T	P109H	1.000
1:31910112:C:A	R107S	1.000
1:31910112:C:G	R107S	1.000
1:31911696:C:A	R107M	1.000
1:31911696:C:G	R107T	1.000
1:31911699:C:A	G106V	1.000
1:31911699:C:T	G106E	1.000
1:31911700:C:G	G106R	1.000
1:31911700:C:T	G106R	1.000
1:31911702:A:G	L105S	1.000
1:31911705:C:A	G104V	1.000
1:31911705:C:T	G104E	1.000
1:31911706:C:G	G104R	1.000
1:31911706:C:T	G104R	1.000
1:31911713:A:C	C101W	1.000
1:31911714:C:T	C101Y	1.000
1:31911715:A:G	C101R	1.000
1:31911723:G:T	A98E	1.000
1:31911775:A:G	W81R	1.000

dbSNP variants (sampled 300 via entrez): RS1000021497 (1:31939283 G>A), RS1000116051 (1:31938323 G>A,C), RS1000197062 (1:31914945 A>G), RS1000233146 (1:31914620 G>T), RS1000282597 (1:31926807 T>C), RS1000417986 (1:31907610 C>A), RS1000517241 (1:31915736 C>T), RS1000562638 (1:31930161 A>AC), RS1000570900 (1:31906247 G>A), RS1000589406 (1:31912729 T>C), RS1000713760 (1:31922667 T>A), RS1001065165 (1:31909499 C>T), RS1001149457 (1:31919366 T>A,C), RS1001151776 (1:31906424 C>A,T), RS1001329221 (1:31940281 T>C)

Disease associations

OMIM: gene MIM:601584 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005951_36	Body mass index	9.000000e-10
GCST90000025_911	Appendicular lean mass	4.000000e-21

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1075105 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 27,049 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL55	PENTAMIDINE	4	27,049

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

6 potent at pChembl≥5 of 8 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.28	IC50	52	nM	CHEMBL4445621
6.89	IC50	130	nM	CHEMBL3393171
6.56	IC50	277	nM	CHEMBL3393171
6.55	IC50	280	nM	CHEMBL3393171
6.52	IC50	300	nM	PENTAMIDINE
6.50	IC50	314	nM	CHEMBL1088572

PubChem BioAssay actives

6 with measured affinity, of 37 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
7-imino-2-phenylthieno[3,2-c]pyridine-4,6-dione	1634316: Inhibition of PTP4A2 (unknown origin) expressed in Escherichia coli assessed as reduction in hydrolysis using DIFMUP as substrate incubated for 30 mins in presence of DTT by Fluorescence based method	ic50	0.0520	uM
7-amino-2-phenyl-5H-thieno[3,2-c]pyridin-4-one	1759059: Inhibition of human His6-tagged PRL-2 expressed in Escherichia coli using TAMRA-Thr-Ala-Asp-Ile-Tyr(PO3H2)-Glu-NH2 peptide as substrate by IMAP-FP assay	ic50	0.1300	uM
Pentamidine	1634309: Inhibition of PTP4A2 (unknown origin)	ic50	0.3000	uM
sodium [6-(2-fluorophenyl)-5,8-dihydro-[1,3]dioxolo[4,5-g]quinolin-8-yl] hydrogen phosphate	463845: Inhibition of human PTP4A2 by enzyme assay	ic50	0.3140	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	4
Cyclosporine	decreases expression, increases expression	2
Aflatoxin B1	increases methylation	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
bisphenol A	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
beta-methylcholine	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Vehicle Emissions	increases abundance, increases expression	1
Cisplatin	affects reaction, decreases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Piroxicam	affects reaction, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Asbestos, Crocidolite	decreases expression	1
Copper Sulfate	increases expression	1
tert-Butylhydroperoxide	increases expression	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1113384	Binding	Inhibition of human PTP4A2 at 10 uM by enzyme assay	Synthesis and preclinical evaluations of 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one monosodium phosphate (CHM-1-P-Na) as a potent antitumor agent. — J Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.